This project aims to address the question whether the elevated levels of glutamate and other neurotransmitters that have been reported in brain following an ischemic insult are indeed important in the subsequent cascade of events leading to cell death or whether they are merely an expression of generalized energy failure. The studies will examine the temporal pattern of changes in the extracellular concentration of excitatory amino acids (EAA) and glycine following episodes of transient global ischemia in rabbits. Microdialysis will be used to obtain fine resolution measurements of regional brain tissue concentrations of these transmitter substances. The relationship between various physiological variables and pharmacological agents thought to alter neurologic outcome and the release of EEA will be analyzed. These agents will include NMDA antagonists and adenosine agonists. The results of these studies will provide a better understanding of the mechanisms of neurological injury in ischemic hypoxia and will help to resolve some of the questions regarding the therapeutic benefit of various neuroprotective agents and interventions.